Factors that Influence Healthcare Professionals' Intentions towards Biosimilars.

Background: Physicians often prescribe original biologic products to patients who have not used them before and are reluctant to switch to biosimilars. Biosimilars are highly similar versions of already-approved biologics, but healthcare professionals typically hesitate to transition patients from the original products to biosimilars. This study aims to investigate the factors that influence U.S. healthcare professionals' intentions to use biosimilars. Methods: A cross-sectional study was conducted. 510 participants were eligible healthcare professionals (279 physicians and 231 pharmacists). The theory of planned behavior (TPB) is used to identify which factors affect healthcare professionals' intentions. Descriptive statistics, chi-square, and the logistic regression model tested the TPB constructs as predictors of intentions toward biosimilars. Results: Among 279 physicians, most were aged 61 and above, with high (n = 142) and low (n = 137) intentions. Male physicians constituted 71% of the population. Attending physicians (66.3%) showed consistent perceptions towards biosimilars, primarily in the private sector (76.3%). Pharmacists (n = 231), a higher percentage of females demonstrated higher intentions compared to males (35.5% vs. 28.1%); the majority were community pharmacists. Associations between years of practice and intentions were significant. Positive correlations existed between beliefs and intentions, except for normative beliefs. Conclusions: This study revealed diverse attitudes among healthcare professionals towards biosimilars in the USA. Pharmacists and physicians, especially those with limited experience, require ongoing education on biosimilar manufacturing pathways. This education supports the appropriate use of biosimilars and helps standardize federal and state legislation.

Non-adherence and non-persistence with antiretroviral treatment in Belgium: A real-world evaluation using a pharmacy database, 2018-2021.

PURPOSE: To evaluate the real-world rates of non-adherence and non-persistence to antiretroviral therapy (ART) among treatment-naïve adult patients with HIV after a 12-month follow-up period in Belgium. METHODS: A retrospective analysis of longitudinal pharmacy claims was conducted using the Pharmanet database from January 1, 2018, to December 31, 2021. Non-adherence was assessed over 12 months and reported as the proportion of days covered below the 80% threshold. Non-persistence was defined as the first 90-day gap in treatment between the two types of ART dispensed. Poisson regression with robust standard error and Cox proportional hazard models were used to assess the factors associated with non-adherence and non-persistence, respectively. RESULTS: Overall, 2999 patients were initiated on ART between 2018 and 2021. After a 12-month follow-up, the proportions of non-adherence and non-persistence were 35.6% and 15.9%, respectively in 2018, and decreased to 18.7% and 6.8%, respectively in 2021. Non-adherence was higher among women, Brussels residents, and those receiving multiple-tablet regimens (MTRs). Similarly, the prevalence of non-persistence was higher among women and MTR recipients. CONCLUSION: Among treatment-naïve adults with HIV in Belgium, non-adherence, and non-persistence to ART showed improvement over the study period but remained at high levels. Disparities were observed by sex and between geographical regions. Prioritizing strategies targeting women in Brussels and facilitating the transition from MTRs to single-tablet regimens should be emphasized optimize adherence to ART in Belgium.

The Added Value of MRI-Based Targeted Biopsy in Biopsy-Naïve Patients: A Propensity-Score Matched Comparison.

BACKGROUND: Multiparametric Magnetic Resonance Imaging (mpMRI)-based targeted biopsy has shown to be beneficial in detecting Clinically Significant Prostate Cancer (csPCa) and avoiding diagnosis of Non-csPCa (ncsPCa); however, its role in the treatment of biopsy-naïve patients is still under discussion. METHODS: After identifying predictors for the diagnosis of csPCa via Multivariate Logistic Regression Analysis (MLRA), a propensity-score (1:1 nearest neighbor) matched comparison was performed between a Systematic-Only Biopsy (SOB) cohort and a mpMRI-based Combined (systematic + targeted) Biopsy (CB) cohort from two tertiary urologic centers (SOB: Department of Urology, University General Hospital of Heraklion, University of Crete, School of Medicine, Heraklion, Crete, Greece; CB: LKH Hall in Tirol, Austria). Only biopsy-naïve patients were included in the study. The study period for the included patients was from February 2018 to July 2023 for the SOB group and from July 2017 to June 2023 for the CB group. The primary outcome was the diagnosis of csPCa (≥ISUP 2); secondary outcomes were overall cancer detection, the added value of targeted biopsy in csPCa detection, and the reduction in ncsPCa diagnosis with CB compared to SOB. To estimate the Average Treatment effect of the Treated groups (ATT), cluster-robust standard errors were used to perform g-computation in the matched sample. p-values < 0.05 with a two-sided 95% confidence interval were considered statistically significant. RESULTS: Matching achieved well-balanced groups (each n = 140 for CB and SOB). In the CB group, 65/140 (46.4%) patients were diagnosed with csPCa compared to 44/140 (31.4%) in the SOB group (RR 1.48, 95%-CI: 1.09-2.0, p = 0.01). In the CB group, 4.3% (6/140) and 1.4% (2/140) of csPCa cases were detected with targeted-only and systematic-only biopsy cores, respectively. In the CB group, 22/140 (15.7%) patients were diagnosed with ncsPCa compared to 33/140 (23.6%) in the SOB group (RR = 0.67, 95% CI: 0.41-1.08, p = 0.1). When comparing SOB to CB (ATT), the marginal OR was 0.56 (95% CI: 0.38-0.82, p = 0.003) for the diagnosis of csPCa and 0.75 (95% CI: 0.47-1.05, p = 0.085) for the diagnosis of overall cancer (≥ISUP 1). CONCLUSION: The CB approach was superior to the SOB approach in detecting csPCa, while no additional detection of ncsPCa was seen. Our results support the application of mpMRI for biopsy-naïve patients with suspicions of prostate cancer.

Management of treatment-naïve diabetic macular edema patients: Review of real-world clinical data.

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.

Decreasing Opioid Addiction and Diversion Using Behavioral Economics Applied Through a Digital Engagement Solution: Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted. OBJECTIVE: Leveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT). METHODS: A team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery. RESULTS: This study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024. CONCLUSIONS: Through this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record. TRIAL REGISTRATION: ClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52882.

Real-World Study on Effectiveness of Insulin Glargine U300 After Oral Antidiabetic Drug Failure in Patients with Type 2 Diabetes in the Gulf Region.

INTRODUCTION: The effectiveness and safety of long-acting insulin glargine U300 (Gla-300), in patients with type 2 diabetes mellitus (T2DM) requiring insulin, has not been reported in the Gulf region. METHODS: Insulin-naïve patients with T2DM, uncontrolled on OADs, and prescribed Gla-300 were followed up in a 12-month prospective observational study. Gla-300 was titrated to glycemic targets. The primary endpoint (achieving glycemic targets) was evaluated at month 6 of treatment. The need for treatment intensification, safety, and patient-reported outcomes (PRO) were also reported. RESULTS: The study included 412 patients (61.7% men; age 52.2 ± 11.1 years and T2DM duration 10.7 ± 6.8 years). Almost 50% were on more than 3 OADs, mostly biguanides, sulfonylureas, and dipeptidyl-peptidase-4 inhibitors. Baseline HbA1c level was 9.2% ± 1.1% and targets were set at 6.9% ± 0.4%. Baseline fasting plasma glucose was 11.5 ± 3.8 mmol/l. Fifty-seven patients (13.8%) achieved glycemic targets at month 6, hindered by baseline HbA1c ≥ 10%, frequent co-morbidities, older age, suburban/rural residence, and full-time employment. Levels of HbA1c dropped progressively by 0.96% ± 0.07% (month 3), 1.29% ± 0.08% (month 6), and 1.76% ± 0.06% (month 12). Gla-300 dose was 17.0 ± 9.0 IU/day at baseline, 24.6 ± 9.6 IU/day at month 3, 28.5 ± 9.9 IU/day at month 6, and 30.7 ± 10.7 IU/day at month 12. Three patients experienced non-severe hypoglycemia and a slight decrease in body weight and PROs improved. CONCLUSIONS: In the Gulf, Gla-300 in patients with T2DM uncontrolled on OADs improved glycemic control, with low rates of hypoglycemia and improved PROs. Gla-300 dose up-titration from baseline to month 6 did not, however, result in a vast proportion of patients achieving their pre-determined HbA1c targets. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03703869.

Dysfunction of neurotransmitter metabolism is associated with the severity of depression in first-diagnosed, drug-naïve depressed patients.

BACKGROUND & AIMS: Biochemical changes of neurotransmitters underlying major depressive disorder (MDD) are unknown. This study preliminarily explored the association between neurotransmitters with MDD and the possibility of objective laboratory prediction of neurotransmitter involvement in MDD. METHODS: A total of 87 first-diagnosed, drug-naïve patients with depression and 50 healthy controls (HCs) were included in the cross-sectional study. The levels and turnovers of neurotransmitters (glutamine (GLN), glutamic acid (GLU), γ-2Aminobutiric acid (GABA), kainate (KA), vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid (HVA), dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA)) were determined and the confounding factors were adjusted. Then a correlation and a predictive analysis towards neurotransmitters for MDD were performed. RESULTS: After adjusting confounding factors, GLU (OR = 1.159), (GLU+ GABA)/GLN (OR = 1.217), DOPAC (OR = 1.106), DOPAC/DA (OR = 1.089) and (DOPAC+ HVA)/DA (OR = 1.026) enacted as risk factors of MDD, while KYN (OR = 0.992) was a protective factor. GABAergic and TRPergic pathways were associated with severity of depressive and anxiety symptoms in patients with depression. The predictive model for MDD (AUC = 0.775, 95%CI 0.683-0.860) consisted of KYN (OR = 0.990) and (GLU + GABA)/GLN (OR = 4.101). CONCLUSIONS: First-diagnosed, drug-naïve depression patients showed abnormal neurotransmitter composition. GLU, (GLU + GABA)/GLN, DOPAC, DOPAC/DA and (DOPAC + HVA)/DA were risk factors of MDD, while KYN was a protective factor. GABAergic and TRPergic pathways were correlated with MDD clinical characteristics. KYN and (GLU + GABA)/GLN may have a predictive value for MDD.

Spinal Cord Stimulation Meets Them All: An Effective Treatment for Different Pain Conditions. Our Experience and Literature Review.

IntroductionSpinal Cord Stimulation (SCS) is an emerging minimally invasive technique which uses neuromodulation to manage different forms of intractable pain. SCS is a well-established option for the treatment of various pain conditions, and nowadays, indications are ever increasing.Materials and MethodsIn this study, we present our case series of 49 patients who underwent SCS at our Institution for the treatment of pain from different etiologies, and discuss our 10-year experience in SCS. For the purpose of this study, we also performed a systematic review of current indications and new perspectives in SCS.ResultsAmong our case series, patients were differentiated into two groups upon prior spinal surgery: patients who had undergone prior spinal surgery for back pain were defined as the "FBSS (failed back surgery syndrome) group," instead patient suffering from different types of pain but who had never undergone surgery were defined as the "naive group." As regards clinical response to SCS, 20 patients out of 36 (55.56%) were classified as responders in the FBSS group; in the "naïve" group, 10 patients out of 13 (76.92%) were classified as responders. Among the "not responders" group, several patients suffered from infections.Of the recent literature about SCS, 2124 records were screened and 37 studies were finally included in the qualitative synthesis for our systematic review.DiscussionIn case of FBSS, surgical revision is often associated with a high morbidity and corresponding low rates of success. Unfortunately, patients affected by chronic pain often become refractory to conservative treatments. Spinal Cord Stimulation (SCS) is nowadays considered as an effective therapy for several chronic and neuropathic pain conditions, such as failed back surgery syndrome. As regards the economic impact of SCS, implantation of an SCS system results in short-term costs increase, but the annual cumulative costs decrease during the following years after implantation, when compared to the costs of conventional management. Beyond the application for the treatment of FBSS, SCS has also been used for the treatment of other types of chronic non-oncological pain such as neuropathic pain and chronic back pain ineligible for surgical intervention. This evidence paved the way to establishing the potential role of SCS also for the treatment of oncological pain. However, the effectiveness and relative safety of SCS for cancer-related pain has not yet been adequately established.ConclusionsSpinal Cord Stimulation is a well-established treatment option in for FBSS. Beyond that, SCS has also been used for the treatment of "naive" patients, suffering from other types of chronic, both oncological and non-oncological, medical-refractory pain such as neuropathic pain and chronic back pain ineligible for surgical intervention.

Allogeneic Serum Eye Drops: A Randomized Clinical Trial to Evaluate the Clinical Effectiveness of Two Drop Sizes.

INTRODUCTION: Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs). METHODS: In a randomized trial, patients with DED first receive micro-sized SEDs (7 µl/unit) for 1 month, followed by a 1-month washout, before receiving conventional-sized SEDs (50 µl/unit) for 1 month; or vice versa. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary endpoints were tear break-up time (TBT), tear production (TP), and presence of corneal punctate lesions (CP). The user-friendliness of both application systems was also compared. A linear mixed model for cross-over design was applied to compare both treatments. RESULTS: Forty-nine patients completed the trial. The mean OSDI score significantly improved from 52 ± 3 to 41 ± 3 for micro-sized SEDs, and from 54 ± 3 to 45 ± 3 for conventional-sized SEDs. Non-inferiority (margin = 6) of micro-sized SEDs was established. We demonstrate a significant improvement for TBT in case of conventional-sized SEDs and for CP in both treatment groups. TP trended towards an improvement in both treatment groups. The user-friendliness of the conventional drop system was significantly higher. CONCLUSIONS: For the first time, non-inferiority of micro-sized allogeneic SEDs was established. The beneficial effect of both SED volumes was similar as measured by the OSDI score. Although user-friendliness of the micro drop system was significantly lower, it is an attractive alternative as it saves valuable donor serum. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03539159).

Association of Blood Levels of Vitamin D and Its Binding Protein with Clinical Phenotypes of Multiple Sclerosis.

BACKGROUND: Low vitamin D levels may synergize with changing levels of the vitamin D binding protein (DBP) to precipitate in the development and clinical progression of multiple sclerosis (MS). In this study, this hypothesis was explored in groups of Kuwaiti healthy controls and patients with different clinical phenotypes of MS. METHODS: Fasting serum concentrations of 25-hydroxyvitamin D [25(OH)D] and DBP were measured in 146 healthy controls and 195 patients with MS. The latter were classified according to the duration, type, and onset of the disease and the mode of treatment. Factors such as relapse/remitting, and the use of nutritional supplements were also considered. RESULTS: The DBP levels were significantly lower in the patients than in the controls. This was more evident in newly diagnosed drug-naïve patients than in those patients with more established MS. MS status and severity were negatively impacted by concurrently low levels of 25(OH)D and DBP. This was most clearly expressed in drug-naïve patients and in those with a disease in relapse. It was also established that the 25(OH)D level had a significant positive correlation with the duration of the disease. CONCLUSION: Lower levels of 25(OH)D and DBP appear to have a synergistic effect on MS status. This was most clearly demonstrated in patients who were newly diagnosed (drug-naïve) and in those patients who were in relapse.

Factors Associated with Prolonged Opioid Use after CMC Arthroplasty.

Background Higher rates of prolonged opioid use have been reported in patients who undergo thumb carpometacarpal (CMC) arthroplasty compared with other hand procedures. Therefore, the aim of this study is to identify the risk factors associated with prolonged postoperative opioid use after CMC arthroplasty, along with reporting the number of patients who filled an opioid prescription more than 30 days postoperatively. Materials and Methods Retrospectively, 563 opioid-naïve patients who underwent CMC arthroplasty were included. A manual chart review was performed to collect patient characteristics, and opioid use was determined based on opioid prescription by a physician. Prolonged opioid use was defined as an opioid prescription at 90 to 180 days postoperatively. A multivariable analysis was performed to identify independent factors associated with an opioid prescription at 90 to 180 days postoperatively. Patients had a median age of 60.4 years (interquartile range [IQR]: 55.5-66.9) and had a median follow-up of 7.6 years (IQR: 4.3-12.0). Results The rates of postoperative opioid use ranged from 6.2% (53 out of 563 patients) at 30 to 59 days postoperatively to 3.9% (22 out of 563 patients) at 150 to 180 days postoperatively. In total, 17.1% (96 out of 563 patients) received a second opioid prescription more than 30 days following surgery, of which 10.8% (61 out of 563 patients) were between 90 and 180 days postoperatively. Older age, defined as a median of 63 years (IQR: 57.10-69.88) ( p = 0.027, odds ratio [OR] = 1.04) and a history of psychiatric disease ( p = 0.049, OR = 1.86) were independently associated with prolonged opioid use. Conclusion A prolonged opioid use rate of roughly 11% was found in opioid-naïve patients who underwent CMC arthroplasty. In patients at risk (older patients or psychiatric history) of prolonged opioid use, careful postoperative pain management is recommended.

Mediators between sexual abuse and eating disorder severity: A comparative case-control study in treatment-naïve patients.

OBJECTIVE: Sexual abuse is associated with eating disorders (EDs) severity. However, the psychological mediators of this association have received scant attention in the literature. METHOD: The present study aimed to evaluate the mediating role of psychological maladjustment, alexithymia, and self-esteem in the relationship between sexual abuse and EDs severity in a sample of 134 treatment-naïve patients with an EDs and 129 paired healthy controls. RESULTS: In the EDs group, EDs severity among participants who had been sexually abused was mediated by greater psychological maladjustment and alexithymia (indirect effects: ß = 12.55, 95% CI [6.11-19.87] p < 0.001; ß = 3.22, 95% CI [0.235-7.97] p < 0.05, respectively). By contrast, these variables had no significant mediating effect on EDs severity in the control group. DISCUSSION: These findings support the hypothesis of a disorder-related relationship between sexual abuse and alexithymia and psychological maladjustment, which, in turn, influences EDs severity. Alexithymia and psychological maladjustment appear to be promising therapeutic targets for patients with EDs who have a history of sexual abuse.

Cardiac wasting in head and neck cancer and in cardiac autopsies from different cancer types: A study in a chemo-naïve setting.

BACKGROUND: Cardiac wasting is a detrimental consequence of cancer that has been traditionally ignored and often misinterpreted as an iatrogenic effect. METHODS: We conducted a retrospective study on 42 chemo-naive patients affected by locally advanced head and neck cancer (HNC). Based on unintentional weight loss, patients were divided into cachectic and non-cachectic. Left ventricular mass (LVM), LV wall thickness (LVWT), interventricular septal (IVS) thickness, left ventricular internal diameter diastolic (LVIDd), left ventricular internal diameter systolic (LVIDs), internal ventricular septum diastolic (IVSd), left ventricular posterior wall thickness diastolic (LVPWd) and LV ejection fraction (LVEF) were analysed by echocardiography. In parallel, we retrospectively analysed 28 cardiac autoptic specimens of patients who either died of cancer before chemotherapy or with a diagnosis of cancer at autopsy. Presence or absence of myocardial fibrosis at microscopic observation was used for sample stratification. Conventional histology was performed. RESULTS: Cachectic and non-cachectic patients had a significantly different value of LVWT and IVS thickness and LVPWd. LVWT was 9.08 ± 1.57 versus 10.35 ± 1.41 mm (P = 0.011) in cachectic and non-cachectic patients, IVS was 10.00 mm (8.50-11.00) versus 11.00 mm (10.00-12.00) (P = 0.035), and LVPWd was 9.0 (8.5-10.0) and 10.00 mm (9.5-11.0) (P = 0.019) in cachectic and non-cachectic patients. LVM adjusted for body surface area or height squared did not differ between the two populations. Similarly, LVEF did not show any significant decline. At multivariate logistic regression analysis for some independent predictors of weight loss, only LVWT maintained significant difference between cachectic and non-cachectic patients (P = 0.035, OR = 0.240; P = 0.019). The secondary analysis on autoptic specimens showed no significant change in heart weight, whereas LVWT declined from 9.50 (7.25-11.00) to 7.50 mm (6.00-9.00) in cardiac specimens with myocardial fibrosis (P = 0.043). These data were confirmed in multivariate logistic regression analysis (P = 0.041, OR = 0.502). Histopathological analysis confirmed severe atrophy of cardiomyocytes, fibrosis and oedema as compared with controls. CONCLUSIONS: Subtle changes in heart structure and function occur early in HNC patients. These can be detected with routine echocardiography and may help to select appropriate cancer treatment regimens for these patients. Histopathological analysis provided conclusive evidence that atrophy of cardiomyocytes, oedema and fibrosis occur during cancer progression and may precede the onset of overt cardiac pathology. To our knowledge, this is the first clinical study that establishes a direct relationship between tumour progression and cardiac remodelling in HNCs and the first pathological study conducted on human cardiac autopsies from selected chemo-naïve cancer patients.

Case Series of HIV-Associated Oral Lesions Among Antiretroviral-Naive Patients During the COVID-19 Pandemic.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has a serious impact on HIV-infected individuals due to limited access to treatment services. This report aimed to describe four cases of oral lesions in HIV-infected antiretroviral-naive patients found during the COVID-19 pandemic. Case: Four patients, males, with an age ranged from 29 to 53 years, came to Oral Medicine Department with chief complaints of lesions on their mouth. They had postponed their visit to healthcare services due to limited access during pandemic. Three patients had just been diagnosed with HIV and had not yet received anti-retrovirus, while 1 patient had not yet been detected with HIV. From the clinical examination and laboratory findings, we diagnosed the lesions with mucous patches, chronic atrophic candidiasis, angular cheilitis, necrotizing ulcerative gingivitis, linear gingival erythema, cytomegalovirus-associated ulcers, and oral hairy leukoplakia. Case Management: We gave chlorhexidine gluconate 0.2% mouthwash for mucous patches, nystatin oral suspension for chronic atrophic candidiasis, miconazole cream 2% for angular cheilitis, debridement with hydrogen peroxide 1.5% and rinsed with normal saline for necrotizing ulcerative gingivitis, and diphenhydramine hydrochloride and 0.2% chlorhexidine gluconate for CMV ulcers. All patients showed good clinical improvement after the treatments. Conclusion: Oral lesions are still commonly found in HIV-infected patients during COVID-19 pandemic. Dentists remain to have a crucial role in the early diagnosis and treatment of HIV-associated oral lesions during COVID-19 pandemic that will have an impact on HIV treatments, also in implementing the Bali Declaration on oral health in HIV/AIDS 2019 to support UNAIDS goal to end AIDS by 2030.

Anti-hyperglycemic effects of propolis or metformin in type 2 diabetes mellitus.

Background: The aim of this study was to evaluate the effect of propolis or metformin versus placebo on glycemic control in pharmacological treatment-naïve patients with type 2 diabetes mellitus (T2DM). Methods: A double-blind, randomized, placebo-controlled in parallel groups clinical trial was performed in 36 pharmacological treatment-naïve patients with T2DM. They received propolis (300 mg), metformin (850 mg), or placebo twice daily before breakfast and dinner for 12 weeks. At the beginning and end of the study, fasting plasma glucose (FPG), 2-h postload glucose (2-h PG) during a 75-g oral glucose tolerance test, glycated hemoglobin A1c (A1C) and a metabolic profile were measured. Areas under the curve (AUC) of glucose and insulin, total insulin secretion (insulinogenic index), the first phase of insulin secretion (Stumvoll index), and insulin sensitivity (Matsuda index) were calculated. Statistical analyses: Kruskal-Wallis, Mann-Whitney U and Wilcoxon tests. Results: The propolis and metformin groups exhibited significant reductions in FPG (p=0.009 and p=0.001, respectively), 2-h PG (p=0.034 and p=0.001, respectively) levels, AUC of insulin, Stumvoll index, and an increment in the Matsuda index. The comparison of the changes from baseline to the end showed significant differences between placebo and propolis in FPG (p=0.004) and A1C (p=0.049) levels, while between placebo and metformin were in FPG (p=0.002), 2-h PG (p=0.004) and A1C (p=0.007) levels. Conclusions: The administration of propolis and metformin compared to placebo reduced FPG and A1C levels; in addition, metformin decreased 2-h PG, AUC of glucose and insulin, high-density lipoprotein cholesterol, and increased the insulin sensitivity.

Abnormal erythrocyte fatty acid composition in first-diagnosed, drug-naïve patients with depression.

BACKGROUND & AIMS: The correlation between fatty acids (FAs) and depression is not yet conclusive. This study examined the relationship of FAs composition with the presence and clinical characteristics of first-diagnosed, drug-naïve patients with depression. METHODS: A total of 139 first-diagnosed, drug-naïve patients with depression and 55 healthy controls (HCs) were included in the cross-sectional study. The levels of erythrocyte membrane FAs were compared and then the correlation between clinical symptoms and fatty acid levels in depression was investigated. RESULTS: Compared to HCs, patients with depression had higher C18:1n9t (z = -2.033, p = 0.042), C20:4n6 (z = -2.104, p = 0.035), C20:3n6 (z = -2.104, p = 0.035) and n-6 polyunsaturated fatty acids (PUFAs) (z = -2.127, p = 0.033), whereas the levels of C18:1n9c (z = -3.348, p = 0.001) were significantly lower. Higher C20:3n6, C20:4n6, C18:1n9t and n-6 PUFAs levels were associated with higher severity of depressive and anxiety symptoms in patients with depression, and the correlation remained after adjusting for the related confounding factors (p < 0.05). CONCLUSIONS: Patients with first-diagnosed, drug-naïve depression show abnormal erythrocyte fatty acid composition. Trans fatty acids (TFAs) and n-6 PUFAs levels are closely related to clinical characteristics of depression. This study indicated that increased n-6 PUFAs and TFAs are characteristic changes of first-diagnosed, drug-naïve depression.

Effectiveness of Dupilumab in the Treatment of Patients with Uncontrolled Severe CRSwNP: A "Real-Life" Observational Study in Naïve and Post-Surgical Patients.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents 25−30% of all CRS cases, and in the most severe forms it is associated with a poor quality of life and a high rate of nasal polyps' recurrence after surgery. Dupilumab has been suggested as a treatment option for severe CRSwNP. Methods: Patients with severe CRSwNP receiving dupilumab from January 2021 were followed up at 1, 3, 6, 9 and 12 months from the first administration and were considered for this study. At baseline and at each follow-up, patients underwent nasal endoscopy and completed the Sinonasal Outcome Test (SNOT)-22, a Visual Analogue Scale (VAS) for smell/nasal obstruction, the Nasal Congestion Score and the Asthma Control Test. Peak nasal inspiratory flow (PNIF), a smell test, nasal cytology and blood eosinophilia were also evaluated. Results: Forty-seven patients were included in the study. Of these, 33 patients had a history of previous surgery (ESS) and had recurrent nasal polyps, while 14 patients were naïve to nasal surgery. Both subjective and objective parameters improved after biological treatment and were correlated with each other (p < 0.05), except for the SNOT-22 and the nasal polyp's score. No correlations were found between nasal and blood eosinophilia. No differences were observed when comparing the post-surgical and the naïve groups. Conclusions: Dupilumab improves nasal obstruction and the sense of smell and reduces the level of local inflammation in severe CRSwNP patients in a similar way in both naïve and post-surgical patients.

Metabolic syndrome and its components among HIV/AIDS patients on Antiretroviral Therapy and ART-Naïve Patients at the University of Calabar Teaching Hospital, Calabar, Nigeria.

Background: Although an increasing access to ART in sub-Saharan Africa has made it possible for HIV/AIDS patients to live longer, clinicians managing such patients are faced with the challenge of drug-related metabolic complications. Methods: A cross -sectional study was carried out at the University of Calabar Teaching Hospital, Nigeria, on three groups of participants; namely HIV patients on ART, ART-naïve patients and HIV negative subjects (n =75). Demographic and anthropometric data were collected using a well-structured questionnaire while biochemical parameters were measured using colorimetric methods. Results: The highest prevalence of MS was associated with the HIV/AIDS patients on ART (i.e. 32.0 %, and 50.3% for NCEP-ATP III and IDF criteria respectively). Patients on ART had significant increases (p< 0.05) in waist to hip ratio, FPG, serum TG and LDL-c; and a significantly higher (p< 0.05) prevalence of hypertension, diabetes, low HDL-c and hypertriglyceridaemia compared to the ART-naïve patients. Low serum HDL-c was the most prevalent form of dyslipidaemia in all three groups and the most prevalent component of MS in HIV patients. Conclusion: ART increases the risk of MS and CVD. HIV/AIDS patients on ART should be advised on lifestyle modifications and undertake regular assessment of their cardiovascular risk factors.

Gut microbiota in mucosa and feces of newly diagnosed, treatment-naïve adult inflammatory bowel disease and irritable bowel syndrome patients.

The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD (Crohn's disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae, in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister, and Adlercreutzia as potential biomarkers of the disease.

Early use of fingolimod is associated with better clinical outcomes in relapsing-remitting multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease with huge heterogeneity in terms of clinical course, disease severity and treatment response. The need for a tailored treatment approach has emerged over the last few years. The present observational study aims to assess fingolimod (FTY) effectiveness in RRMS patients, stratifying them according to the disease-modifying treatments used before FTY, to identify subjects who could benefit more from this treatment. METHODS: We prospectively included 554 RRMS patients who started FTY at San Raffaele Hospital between 2012 and 2018. We classified them into three categories according to previous treatments: naïve patients, subjects previously treated with first-line drugs, and patients previously treated with second-line drugs. We compared disease activity during a 2-years follow-up using No-Evidence-of-Disease-Activity (NEDA-3) and Time-To-First-Relapse (TTFR) outcomes, applying logistic and Cox proportional hazard regression respectively. RESULTS: The proportion of patients who maintained NEDA-3 status was higher in the naïve group despite a higher level of baseline disease activity (naïve versus first-line p = 0.025, naïve versus second-line p < 0.001). In the multivariable analyses, patients switching to FTY from first- and second-line treatments showed a higher risk of disease reactivation (p = 0.041, OR = 1.86 and p = 0.002, OR = 2.92, respectively) and a shorter TTFR (p = 0.017, HR = 4.35 and p = 0.001, HR = 8.19, respectively). CONCLUSION: Naïve patients showed a better response to FTY compared to patients switching to FTY from other drugs. Our findings support the early use of FTY in patients with active MS.